By directly manipulating the brains of sleeping mice, researchers tricked the animals into thinking they had received a reward at a specific place.
Photograph: Hattie Spray/PA

Neuroscientists in France have implanted false memories into the brains of sleeping mice. Using electrodes to directly stimulate and record the activity of nerve cells, they created artificial associative memories that persisted while the animals snoozed and then influenced their behaviour when they awoke.

Manipulating memories by tinkering with brain cells is becoming routine in neuroscience labs. Last year, one team of researchers used a technique called optogenetics to label the cells encoding fearful memories in the mouse brain and to switch the memories on and off, and another used it to identify the cells encoding positive and negative emotional memories, so that they could convert positive memories into negative ones, and vice versa.

The new work, published today in the journal Nature Neuroscience, shows for the first time that artificial memories can be implanted into the brains of sleeping animals. It also provides more details about how populations of nerve cells encode spatial memories, and about the important role that sleep plays in making such memories stronger.

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Karim Benchenane of the French National Centre for Scientific Research (CNRS) in Paris and his colleagues implanted electrodes into the brains of 40 mice, targeting the medial forebrain bundle (MFB), a component of the reward circuitry, and the CA1 region of the hippocampus, which contains at least three different cell types that encode the memories needed for spatial navigation.

They then left the mice to explore their surroundings, and monitored the responses of their hippocampal neurons to identify place cells, each of which fired when one of the animals was in a specific location, or ‘place field’, within its environment. In one experiment, performed on five awake animals, they timed electrical stimulation of the MFB to coincide with the firing of a given place cell.

This paired stimulation protocol created a false associative memory in the animals’ brains. The mice linked MFB stimulation with the place field encoded by the cell, and subsequently spent 4- to 5-times more time in that specific location than two control mice who received MFB stimulation that did not coincide with place cell firing.

Place cells are known to ‘replay’ their activity patterns during sleep, and this is believed to strengthen newly formed memories, possibly by promoting the formation of new synaptic connections. Nevertheless, we still don’t know what place cells are doing during replay, or exactly how replayed activity is related to their navigational functions.

To investigate further, the researchers repeated their experiments in five sleeping mice. Having previously identified place cells while they explored their surroundings, the researchers allowed the animals to doze off, and then paired the firing of a selected place cell in each one with stimulation of the MFB. Later on, these animals, too, showed a strong preference for that given place field, heading directly for it when they woke up and spending far more time there than in other locations.

By contrast, the control mice, which received ‘random’ MFB stimulation that was not paired with the firing of a place cell, either while awake or during sleep, wandered around aimlessly, with no preference for any particular place.

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“This is exciting because it provides excellent evidence for the importance of place cells in guiding navigation to goals,” says Hugo Spiers, a spatial cognition researcher at UCL. “It is also remarkable that the authors have been able to incept a false memory into the brain during sleep using this method.”

As well as demonstrating that place cells encode the same kind of information during sleep as they do in wakefulness, and that this is important for navigation, the new findings also provide clues about how the sleeping brain strengthens new memories. Most of the paired stimulations that created false memories were carried out during slow wave stages of sleep, adding weight to the hypothesis that oscillatory activity patterns called sharp wave ripples are necessary for the memory consolidation during sleep.

This study involved implanting recording and stimulating electrodes directly into the animals’ brains, a highly invasive procedure. It’s therefore unlikely that the method would ever be used in humans, except under very special circumstances, such as the experiments performed during pre-surgical evaluation of patients with drug-resistant epilepsy.

Even so, other work – most notably that of psychologist Beth Loftus – shows that false memories can be implanted into the human brain without the use of sophisticated technology. In one recent study, nearly three-quarters of participants reported having rich false memories of a crime they did not commit.

Research clearly shows that stress and sleep deprivation can make people more susceptible to false memories, and this has major implications for the use of so-called ‘enhanced interrogation techniques’. By providing a clearer picture of the brain activity associated with the formation of false memories, studies like this one could eventually help researchers to find ways of making us less prone to them - and new ways of creating them more effectively, too.